During the past year we have :(i) discovered that mice lacking uteroglobin, a potent phospholipase A2 (PLA2) inhibitor, develop a severe glomerulopathy characterized by heavy deposition of multimeric fibronectin (Fn) and collagen. This phenotype in mice is virtually identical to that of a human hereditary Fn-deposit glomerulonephritis. Studies in progress will delineate whether the human disease is due to mutations in the UG or its receptor gene; (ii) one hundred percent of the animals (n=16) studied so far developed cancer, suggesting a tumor-suppressor-like role of UG; (iii) uteroglobin regulates cell motility via a high-affinity receptor, expressed on several normal and cancer cell types; (iv) induced overexpression of UG in tumor cells reverses their transformed phenotype and this reversal requires both UG as well as its receptor; (iii) isolated and characterized mouse palmitoyl-protein thioesterase (mPPT) cDNA and the gene, respectively, and deciphered a temporal pattern suggesting that the expression of this gene in the retina precedes that in the brain during development, explaining in part, why the loss of vision occurs earlier than the deterioration of brain function in infantile neuronal ceroid lipofuscinosis (INCL); (iv) partial characterization of the mPPT gene has been achieved in order to generate the targeting construct for developing an animal model for INCL, an uniformly fatal disease in children that has no effective therapy; (v) isolated and partially characterized the human ceramidase gene, mutations of which causes an autosomal recessive disease known as Farber lipogranulomatosis; (vi) characterized a high-affinity cell surface receptor for group I phospholipase A2 (PLA2) and found that via this receptor sPLA2-I induces cellular invasion of the extracellular matrix and this receptor is expressed at a high level in several tumor cell lines; (v) demonstrated a critical role of nuclear factor IL6 (NF IL-6) in the induction of sPLA2-I receptor-mediated activation of the cyclooxygenase-2 (COX-2) gene expression in MC-3T3 and human colorectal adenocarcinoma cell lines; (vii) cloned and characterized a cDNA and the gene for murine group I pancreatic PLA2 and its differential tissue-specific expression in the mouse; (viii) discovered that sPLA2-I gene expression is drastically down-regulated in colorectal cancer tissues and in the colon of Min (multiple intestinal neoplasia) mouse, an animal model for familial adenomatous polyposis (FAP) and heritable colorectal cancer in humans suggesting a modifier role of sPLA2-I in this disease.